20.500.12556/DiRROS-30005 Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axis Glioblastoma (GB) is an aggressive primary brain cancer with poor patient prognosis. Natural killer (NK) cells can recognise and eliminate a range of malignant cells, including GB stem cells, which drive GB recurrence. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, but a better understanding of the complex crosstalk between GB and NK cells is needed, particularly within the immunosuppressive GB tumour microenvironment. In this study, we established a reproducible protocol for the production and dynamic culture of uniformly sized GB spheroids using the Celvivo Clinostar system. Our spheroids recapitulated the heterogeneous structure of GB and expressed ligands for NK cell receptors at levels distinct from those observed in corresponding GB cell lines in standard culture, implicating altered sensitivity of GB cells to NK cells in dynamic 3D cultures. GB-NK cell crosstalk was GB cell type dependent and the ability of NK cells to infiltrate GB did not necessarily correlate with their cytotoxicity against GB cells. Spheroids derived from differentiated GB cells secreted higher levels of immunomodulatory cytokines compared to spheroids from GB stem-like cells, and a prominent increase in the secretion of immune-attracting factors was observed in their co-cultures with NK cells. Finally, the CD155-DNAM1/TIGIT axis was indicated as an important regulator of NK cell cytotoxicity against GB stem-like cells. Collectively, our results highlight important factors in GB-NK cell communication and provide a groundwork for further targeted research as well as therapeutic evaluation of NK cell-based approaches in the established dynamic 3D cultures. glioblastoma immunotherapy dynamic in vitro models natural killer cells cytotoxicity 21 infiltration cytokines CD155 glioblastom naravne celice ubijalke modeli raka true false true Angleški jezik Slovenski jezik Neznano 2026-06-11 12:27:54 2026-06-11 12:27:54 2026-06-12 03:54:43 0000-00-00 00:00:00 2026 0 0 Soavtorji: Tina Kolenc Milavec, Pia Žižek, Špela Kladnik, Bernarda Majc, Emanuela Senjor, Milica Perišić Nanut, Andrej Porčnik, Borut Prestor, Urban Švajger, Metka Novak, Barbara Breznik; Nasl. z nasl. zaslona; Opis vira z dne 18. 5. 2026; Str. 1-22 [article no.] 289 Vol. 24 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2026-03-30 577.2 1478-811X 10.1186/s12964-026-02826-y 278556675 https://link.springer.com/article/10.1186/s12964-026-02826-y 1 37ae83a6-6580-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45214 RAZ_Habic_Anamarija_2026.pdf RAZ_Habic_Anamarija_2026.pdf 1 809180A6D1428F16D102CBF385A09F23 9fa3c29f9be9903ef82be55b0f830d64db265f2fefae21b4b1b693ab9dd00d88 55e14e57-6580-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45215 Nacionalni inštitut za biologijo 0 0 0